Diagnostic and prognostic value of growth differentiation factor 15 in suspected functionally relevant coronary artery disease.

BACKGROUND: The rapid and accurate non-invasive diagnosis of significant and functionally relevant coronary artery disease is a crucial yet unmet clinical need. Growth differentiation factor 15 (GDF-15) may be involved in the development of coronary artery disease. We aimed to evaluate the diagnostic and prognostic value of GDF-15 in patients with suspected functionally relevant coronary artery disease. METHODS: In this prospective cohort study, consecutive patients underwent myocardial perfusion imaging with single-photon-emission computed tomography, and coronary angiography plus fractional flow reserve, when available. Functionally relevant coronary artery disease was centrally adjudicated. Prognostic endpoints included all-cause mortality and cardiovascular death. RESULTS: Among 3,379 patients eligible for this analysis (median age 68 years, 33% female, 44% known coronary artery disease), 1,160 patients (34%) had adjudicated functionally relevant coronary artery disease. GDF-15 concentrations were significantly higher in patients with the adjudicated diagnosis (1,325 ng/L (95%CI, 1,258-1,364) versus 1,041 ng/L (95%CI, 1,009-1,074), p<0.001). However, the diagnostic accuracy of GDF-15 for identifying functionally relevant coronary artery disease was modest, with an area under the curve (AUC) of 0.598. Combined with clinical judgment, GDF-15 significantly increased the diagnostic accuracy (AUC 0.659). During a 5-year follow-up, 437 deaths (14%) occurred, of which 231 were cardiovascular. GDF-15 had very high prognostic accuracy for all-cause and cardiovascular death (e.g. time-dependent AUC 0.815 and 0.834 at 2 years), at least comparable to high-sensitivity cardiac troponin (hs-cTn)T, and higher than hs-cTnI. CONCLUSION: While GDF-15 has limited diagnostic utility, it exhibits high prognostic value in patients with suspected functionally relevant coronary artery disease.